Caffeine Induces High Expression of cyp-35A Family Genes and Inhibits the Early Larval Development in Caenorhabditis elegans

Abstract

Intake of caffeine during pregnancy can cause retardation of fetal development. Although the significant influence of caffeine on animal development is widely recognized, much remains unknown about its mode of action because of its pleiotropic effects on living organisms. In the present study, by using Caenorhabditis elegans as a model organism, the effects of caffeine on development were examined. Brood size, embryonic lethality, and percent larval development were investigated, and caffeine was found to inhibit the development of C. elegans at most of the stages in a dosage-dependent fashion. Upon treatment with 30 mM caffeine, the majority (86.1 ± 3.4%) of the L1 larvae were irreversibly arrested without further development. In contrast, many of the late-stage larvae survived and grew to adults when exposed to the same 30 mM caffeine. These results suggest that early-stage larvae are more susceptible to caffeine than later-stage larvae. To understand the metabolic responses to caffeine treatment, the levels of expression of cytochrome P450 (cyp) genes were examined with or without caffeine treatment using comparative micro-array, and it was found that the expression of 24 cyp genes was increased by more than 2-fold (p < 0.05). Among them, induction of the cyp-35A gene family was the most prominent. Interestingly, depletion of the cyp-35A family genes one-by-one or in combination through RNA interference resulted in partial rescue from early larval developmental arrest caused by caffeine treatment, suggesting that the high-level induction of cyp-35A family genes can be fatal to the development of early-stage larvae.

Lifespan Extension Induced by Caffeine in Caenorhabditis elegans is Partially Dependent on Adenosine Signaling

“…Noteworthy, worms exposed to high concentrations of caffeine had an accentuated delay in their larval development and at the highest concentrations, did not develop beyond the first larval stage and died after a couple of days. This outcome suggests that caffeine is toxic at higher concentrations, as reported in the previous study (Min et al, 2015 ), in agreement with the reduction in lifespan of worms exposed to higher levels of it.…”

Caffeine Induces the Stress Response and Up-Regulates Heat Shock Proteins in Caenorhabditis elegans

“…Comparative proteomic analyses were carried out by comparing proteomes extracted from worms grown with or without caffeine to determine the C. elegans protein profile in response to caffeine. We reported previously that high-dose caffeine (30 mM) treatment inhibits C. elegans development and results in early larval stage developmental arrest ( Min et al, 2015 ). Thus, proteomes were prepared from L1-stage worms grown with or without caffeine.…”

“…High-dose caffeine treatment is a developmental stressor because it inhibits the C. elegans development ( Min et al, 2015 ). Here, HSPs were the major stress responding proteins after caffeine treatment ( Table 1 ).…”

“…The RNAi analysis was performed using the “RNAi-by-soaking” method, as described previously ( Min et al, 2015 ).…”

“…In our previous study, we investigated effects of caffeine on Caenorhabditis elegans as an animal model organism. We showed that a high dose (30 mM) of caffeine inhibits early larval development ( Min et al, 2015 ), suggesting that a high dose of caffeine is a developmental stressor. Several reports have demonstrated that caffeine affects C. elegans development in a dose-dependent manner.…”